Vaginal microbiome and sexually-transmitted pathogens in Chinese reproductive-age women: a multicentre cross-sectional and longitudinal cohort study

Sexually transmitted infections (STIs) are associated with vaginal dysbiosis, and co-infections are common but understudied. In this study, 6217 reproductive-age women are recruited from 38 study centres across China at baseline and 2738 participants are followed up at 6 months. We profile the vaginal microbiota by 16S rRNA gene sequencing in conjunction with measurement of nine common STIs. The primary outcome of this study is STI status, and secondary outcome is the risk of cervical lesions. Mycoplasmas hominis (MH) far exceeds other STIs in the association with vaginal microbiota, whereases previously reported associations between Human papillomavirus (HPV) and vaginal dysbiosis might be confounded by the co-infected MH in this study. Both MH infection and increased bacterial diversity are independently associated with increased risk of cervical lesion in HPV-negative women (Shannon, OR (odds ratio) = 1.71, 95% CI (confidence interval) = 1.23-2.36; MH, OR = 2.42 95% CI = 1.36-4.30). These associations are also identified in longitudinal analyses (Shannon, HR (hazard ratio) = 1.72, 95% CI = 1.04-2.86; MH, HR = 2.37, 95% CI = 0.98-5.72). Our findings highlight the importance of considering MH status when studying vaginal microbiota in cervical lesions, and suggest the need for further investigation of microbiota-associated mechanisms in HPV-negative cervical lesions. (ClinicalTrials.gov. NCT04694495).